The Rip11/Rab11-FIP5 and kinesin II complex regulates endocytic protein recycling.
Sorting and recycling of endocytosed proteins are required for proper cellular function and growth. Internalized receptors either follow a fast constitutive recycling pathway, returning to the cell surface directly from the early endosomes, or a slow pathway that involves transport via perinuclear recycling endosomes. Slow recycling pathways are thought to play a key role in directing recycling proteins to specific locations on cell surfaces, such as the leading edges of motile cells. These pathways are regulated by various Rab GTPases, such as Rab4 and Rab11. Here we characterize the role of Rip11/FIP5, a known Rab11-binding protein, in regulating endocytic recycling. We use a combination of electron and fluorescent microscopy with siRNA-based protein knockdown to show that Rip11/FIP5 is present at the peripheral endosomes, where it regulates the sorting of internalized receptors to a slow recycling pathway. We also identify kinesin II as a Rip11/FIP5-binding protein and show that it is required for directing endocytosed proteins into the same recycling pathway. Thus, we propose that the Rip11/FIP5-kinesin-II complex has a key role in the routing of internalized receptors through the perinuclear recycling endosomes.
Schonteich
Eric
E
Department of Cellular and Developmental Biology, School of Medicine, University of Colorado Health Sciences Center, 12801 E. 17th Avenue, Aurora, CO 80045, USA.
Wilson
Gayle M
GM
Burden
Jemima
J
Hopkins
Colin R
CR
Anderson
Keith
K
Goldenring
James R
JR
Prekeris
Rytis
R
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C087415:KIF3A protein, human; C095899:KIF3B protein, human; D024101:Mitochondrial Proteins; C485422:RAB11FIP5 protein, human; D016547:Kinesins